Methadone and Phenobarbital Interaction
Drug interaction information between Methadone and Phenobarbital.
Methadone and Phenobarbital have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Methadone and Phenobarbital. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Both drugs slow down the central nervous system, and taking them together makes this effect much stronger. This can lead to dangerous breathing problems, extreme sleepiness, or even death.
What To Do
Avoid taking these drugs together if possible. If they must be used together, your doctor will need to monitor you very closely for signs of breathing trouble.
FDA Label Information
John’s Wort, Phenobarbital Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death (see WARNINGS ).
Methadone Also Interacts With
- Itraconazole major
- Safinamide major
- Tranylcypromine moderate
- Gabapentin minor
- Sertraline minor
Phenobarbital Also Interacts With
- Nirmatrelvir/Ritonavir major
- Ranolazine major
- Voriconazole major
- Canagliflozin moderate
- Cenobamate moderate
Frequently Asked Questions
Can I take Methadone and Phenobarbital together?
This is a moderate interaction. Avoid taking these drugs together if possible. If they must be used together, your doctor will need to monitor you very closely for signs of breathing trouble.
How serious is the interaction between Methadone and Phenobarbital?
This interaction is classified as "moderate" severity by the FDA. Moderate interactions may worsen your condition or change how your medications work.
Why do Methadone and Phenobarbital interact?
Both drugs slow down the central nervous system, and taking them together makes this effect much stronger. This can lead to dangerous breathing problems, extreme sleepiness, or even death.
Understanding the Methadone and Phenobarbital Interaction
FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Methadone belongs to the Opioid Agonist class and Phenobarbital belongs to the Anticonvulsant (Barbiturate) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Both drugs slow down the central nervous system, and taking them together makes this effect much stronger. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Methadone has 41 total documented interactions on file in this dataset, and Phenobarbital has 59. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Avoid taking these drugs together if possible. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Methadone or Phenobarbital based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.